1. Field of the Invention
The present invention is directed to a novel pharmaceutical composition comprising guaifenesin and a second drug. In particular, the present application is directed to a novel pharmaceutical composition comprising guaifenesin and a second drug which is an antitussive or a decongestant. More particularly, the present application is directed to a composition comprising guaifenesin having both immediate and extended release profiles and codeine having an immediate release profile.
2. Description of Related Art
Compounds such as codeine are known to have both antitussive and pain relieving properties. The antitussive effect occurs at a lower dose than that needed to provide pain relief.
In addition, compounds such as codeine are used in combination with compounds that treat other symptoms of a cough/cold or flu, e.g. expectorants, mucus thinning drugs, decongestants and/or antihistamines. However, a dose of an antitussive compound such as codeine typically provides a therapeutic effect for about 2.5-3 hours, whereas many of the compounds often used with this type of antitussive compound provide therapeutically effective plasma concentrations per dose over a period that is significantly different. For example, a dose of an expectorant such as guaifenesin will usually provide relief for about one hour, and decongestants usually provide relief for about 4 to 8 hours.
As a result, there is little benefit to be gained in combining an antitussive such as codeine with a drug having a shorter or longer therapeutically effective period in a single dosage form. In such a combination, one drug (e.g. codeine) may still provide the desired effect when the other drug has already ceased to be effective, or the other drug may continue to exert its effect, which would prevent administration of a further dose of the antitussive.
It would be desirable if patients suffering from a cough/cold/flu-type conditions, which an antitussive like codeine would provide relief against could be combined with a different drug, such as guaifenesin, in order to obtain relief from symptoms that the antitussive does not treat.
Sustained release pharmaceutical formulations provide a significant advantage over immediate release formulations to both clinicians and their patients. Sustained release dosage forms provide for fewer daily dose administrations than their immediate release counterparts. For example, a standard dosage regimen for a 400 mg immediate release drug with a short half-life, such as guaifenesin, requires administration three times within twelve hours to maintain adequate bioavailability to achieve the desired therapeutic effect.
Besides reducing the frequency of dosing and providing a more consistent therapeutic effect, sustained release dosage forms generally help reduce side effects caused by a drug. Because sustained release dosage forms deliver the drug in slow, incremental amounts versus the cyclic high and low concentrations of immediate release formulations, it is easier for a patient's body to digest the drug, thereby avoiding undesirable side-effects. For patients who self-administer therapies, sustained release dosage forms generally result in greater compliance due to the lower frequency of dosing, lower quantity of dosage units to be consumed, and reduced undesired side-effects.
Generally, sustained release formulations contain drug particles mixed with or covered by a polymer material, or blend of materials, which is resistant to degradation or disintegration in the stomach and/or in the intestine for a selected period of time. Release of the drug may occur by leeching, erosion, rupture, diffusion or similar actions depending upon the nature of the polymer material or polymer blend used.
Furthermore, most formulations that claim twelve hour potency release almost all of their drug within six to eight hours, making the formulation less therapeutically effective towards the end of the twelve hour period. To prevent blood serum concentrations of drug from falling below a therapeutically effective level (Cmin) at extended time periods, many manufacturers increase the drug strength of the dosage form. The increase in drug strength, however, results in a concomitant increase in side-effects.
Other pharmaceutical manufacturers have made tablets and capsules containing a combination of an immediate release formulation and a sustained release formulation to improve the release profile of certain sustained release dosage forms. Although this solution improves the Cmax and length of time before the drug appears in the blood stream in some formulations, the extended therapeutic effect is not improved.
Furthermore, medicaments have different solubility properties and pH dependencies, which affect dissolution rate and bioavailability. Bioavailability can also be affected by a number of factors such as the amounts and types of adjuvants used, the granulation process, compression forces (in tablet manufacturing), surface area available for dissolution and environmental factors such as agitation in the stomach and the presence or absence of food. Due to these numerous factors, specific formulations play an important role in the preparation of prolonged action solid dosage forms, particularly in the preparation of solid dosage forms that achieve appropriate bioavailability for optimum therapeutic effect.
WO 01/082895 discloses a composition which comprises immediate and sustained release portions, both of which contain guaifenesin. WO 03/088952 discloses a composition which also comprises guaifenesin-containing immediate and sustained release. The specification exemplifies compositions which also include dextromethorphan or pseudoephedrine.